Is IGFALS p.Asp51= (c.153C>T) pathogenic?

IGFALS p.Asp51= (c.153C>T) is classified Likely benign in IGFALS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-08-08). Ultra-rare (popmax 0.0223%, eas); Associated with IGFALS-related disorder.

What condition is associated with IGFALS p.Asp51= (c.153C>T)?

IGFALS p.Asp51= (c.153C>T) is associated with IGFALS-related disorder (ClinVar).

How common is IGFALS p.Asp51= (c.153C>T) in the general population?

IGFALS p.Asp51= (c.153C>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

IGFALS p.Asp51=

c.153C>T · rs747677141 · VCV3043074

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Conditions

IGFALS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -3.5
Overall
CADD	3.632	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,860 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00917%

Overall 0.00181% 29/1,601,260 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,486
Middle Eastern	0.0165%	6,050
Admixed American	0.00667%	14,999
Remaining individualsnot grpmax-eligible	0.00321%	31,187
African / African-American	0.00266%	37,524
South Asian	0.0011%	91,052
European (non-Finnish)	0.000763%	131,076

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: IGFALS
Protein: p.Asp51=
Coding: c.153C>T
MANE Select: NM_004970
dbSNP: rs747677141
Type: single nucleotide variant
Location: chr16:1792265 (GRCh38)
Gene constraint: LOEUF 1.908 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 91.13 · 1 PDB
Residue 51: the lrrnt domain

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

Disease context

IGFALS-related disorder

Similar variants

IGFALS p.Asp51Glu Likely benign ★ same residue
IGFALS p.Leu134Gln Pathogenic ★ same condition
IGFALS p.Phe602Cys Likely pathogenic ★ same condition
IGFALS p.Asn492Ser Uncertain significance ★ same condition
IGFALS p.Pro73Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
IGFALS c.17-52C>T Benign same condition
IGFALS p.Gln482= Likely benign same condition
IGFALS p.Glu35fs 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/igfals-p-asp51 (accessed [today's date]).

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