Is GANAB p.Ser14Pro (c.40T>C) pathogenic?

GANAB p.Ser14Pro (c.40T>C) is classified Uncertain significance in GANAB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-06). AlphaMissense: likely benign (0.0748); Very rare (popmax 0.00134%, afr).

How common is GANAB p.Ser14Pro (c.40T>C) in the general population?

GANAB p.Ser14Pro (c.40T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about GANAB p.Ser14Pro (c.40T>C)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

GANAB p.Ser14Pro

c.40T>C · rs762092056 · VCV2053316

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.389	indeterminate
SaProt	LLR -5.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 14 kb · p 0.65 · regional, not allelic
Overall
CADD	18.56	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,776 alleles

Filtering AF 0.00043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000314%

Overall 0.000684% 11/1,609,034 alleles · very rare exomes 9/1,456,864 · genomes 2/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,776
European (non-Finnish)	0.000851%	117,550

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: GANAB
Protein: p.Ser14Pro
Coding: c.40T>C
MANE Select: NM_198334
dbSNP: rs762092056
Type: single nucleotide variant
Location: chr11:62639730 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.43 · 2 PDB

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

Similar variants

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GANAB p.Arg61Ter Pathogenic ★★ same type
GANAB p.Arg812Ter Pathogenic/Likely pathogenic ★★ same type
GANAB p.Arg815Ter Pathogenic/Likely pathogenic ★★ same type
GANAB p.Arg817Trp Likely pathogenic ★★ same type
GANAB p.Gln414Ter Pathogenic/Likely pathogenic ★★ same type
GANAB p.Gln837Ter Pathogenic/Likely pathogenic ★★ 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/ganab-p-ser14pro (accessed [today's date]).

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