Is ASXL3 p.Ser172Pro (c.514T>C) pathogenic?

ASXL3 p.Ser172Pro (c.514T>C) is classified Benign/Likely benign in ASXL3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-25). AlphaMissense: likely pathogenic (0.8133); Rare (popmax 0.311%, afr); Associated with severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome.

How common is ASXL3 p.Ser172Pro (c.514T>C) in the general population?

ASXL3 p.Ser172Pro (c.514T>C) is rare (popmax 0.311%, afr) (gnomAD).

How is Bainbridge-Ropers syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ASXL3 p.Ser172Pro (c.514T>C)?

AlphaMissense predicts likely pathogenic (score 0.8133) — an in-silico prediction, not a clinical call.

ASXL3 p.Ser172Pro

Q: What condition is associated with ASXL3 p.Ser172Pro (c.514T>C)?

ASXL3 p.Ser172Pro (c.514T>C) is associated with severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome (ClinVar).

c.514T>C · rs201872027 · VCV1246157

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8133 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.311%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome

Computational evidence

Protein change
AlphaMissense	0.8133	likely pathogenic
REVEL	0.359	indeterminate
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 105 kb · p 0.066 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.311% African / African-American · 230/74,062 alleles

Filtering AF 0.278% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.265%

Overall 0.017% 267/1,571,046 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.311%	322
Admixed American	0.026%	3,852
Remaining individualsnot grpmax-eligible	0.0197%	5,084
Ashkenazi Jewishnot grpmax-eligible	0.00347%	28,838
South Asian	0.00235%	42,557
European (non-Finnish)	0.000691%	144,614

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ASXL3
Protein: p.Ser172Pro
Coding: c.514T>C
MANE Select: NM_030632
dbSNP: rs201872027
Type: single nucleotide variant
Location: chr18:33670709 (GRCh38)
Gene constraint: LOEUF 0.229 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.70
Residue 172: the 'disordered' region

Full ASXL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bainbridge-Ropers syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Antenatal, Infancy, Neonatal

Similar variants

ASXL3 c.3039+1G>A Pathogenic ★★ same condition
ASXL3 p.Arg1036Ter Pathogenic/Likely pathogenic ★★ same condition
ASXL3 p.Arg1117Ter Pathogenic/Likely pathogenic ★★ same condition
ASXL3 p.Arg1444Ter Pathogenic/Likely pathogenic ★★ same condition
ASXL3 p.Arg1467Ter Pathogenic ★★ same condition
ASXL3 p.Arg1823Ter Pathogenic/Likely pathogenic ★★ same condition
ASXL3 p.Arg63Ter Likely pathogenic ★★ same condition
ASXL3 p.Gln1001Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/asxl3-p-ser172pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown