Is AAGAB p.Ser14Phe (c.41C>T) pathogenic?

AAGAB p.Ser14Phe (c.41C>T) is classified Uncertain significance in AAGAB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: ambiguous (0.5087); Very rare (popmax 0.0067%, eas).

How common is AAGAB p.Ser14Phe (c.41C>T) in the general population?

AAGAB p.Ser14Phe (c.41C>T) is very rare (popmax 0.0067%, eas) (gnomAD).

What do computational predictors say about AAGAB p.Ser14Phe (c.41C>T)?

AlphaMissense predicts ambiguous (score 0.5087) — an in-silico prediction, not a clinical call.

AAGAB p.Ser14Phe

c.41C>T · rs368197105 · VCV2510172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5087 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5087	ambiguous
REVEL	0.105	moderately benign-leaning
SaProt	LLR -12.71	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP -0.16, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 52 kb · p 8.1e-05 · regional, not allelic
Overall
CADD	21.9	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 0.0067% East Asian · 3/44,776 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000435% 7/1,609,668 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0067%	14,925
African / African-American	0.00267%	37,421
Admixed American	0.00167%	59,740
European (non-Finnish)	8.48e-05%	1,179,083

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: AAGAB
Protein: p.Ser14Phe
Coding: c.41C>T
MANE Select: NM_024666
dbSNP: rs368197105
Type: single nucleotide variant
Location: chr15:67254591 (GRCh38)
Gene constraint: LOEUF 1.156 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 3 PDB

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

Similar variants

AAGAB p.Arg124Ter Pathogenic ★★ same type
AAGAB p.Arg161Ter Pathogenic ★★ same type
AAGAB p.Gln21Ter Pathogenic ★★ same type
AAGAB p.Ala74Pro Uncertain significance ★★ ⚠ same type
AAGAB p.Arg161Gln Uncertain significance ★★ ⚠ same type
AAGAB p.Leu92Val Uncertain significance ★★ ⚠ same type
AAGAB c.264+33A>G Benign ★★ same type
AAGAB c.536-95G>A Benign ★★ same type

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/aagab-p-ser14phe (accessed [today's date]).

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