Is GAPVD1 p.Ser112Phe (c.335C>T) pathogenic?

GAPVD1 p.Ser112Phe (c.335C>T) is classified Uncertain significance in GAPVD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-20). AlphaMissense: likely pathogenic (0.7719); Very rare (popmax 0.0011%, sas); Associated with GAPVD1-related disorder.

What condition is associated with GAPVD1 p.Ser112Phe (c.335C>T)?

GAPVD1 p.Ser112Phe (c.335C>T) is associated with GAPVD1-related disorder (ClinVar).

How common is GAPVD1 p.Ser112Phe (c.335C>T) in the general population?

GAPVD1 p.Ser112Phe (c.335C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about GAPVD1 p.Ser112Phe (c.335C>T)?

AlphaMissense predicts likely pathogenic (score 0.7719) — an in-silico prediction, not a clinical call.

GAPVD1 p.Ser112Phe

c.335C>T · rs1288782523 · VCV3029008

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7719 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GAPVD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.7719	likely pathogenic
REVEL	0.716	pathogenic-leaning
SaProt	LLR -8.81	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 25 kb · p 9.9e-05 · regional, not allelic
Overall
CADD	27.3	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 0.0011% South Asian · 1/91,072 alleles

Overall 6.2e-05% 1/1,613,970 alleles · very rare exomes 1/1,461,840 · genomes 0/152,130 · joint denominator

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: GAPVD1
Protein: p.Ser112Phe
Coding: c.335C>T
MANE Select: NM_001282680
dbSNP: rs1288782523
Type: single nucleotide variant
Location: chr9:125302132 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.17

Full GAPVD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GAPVD1-related disorder

Similar variants

GAPVD1 p.Arg1306Trp Uncertain significance ★ ⚠ same condition
GAPVD1 p.Arg487His Uncertain significance ★ ⚠ same condition
GAPVD1 p.Arg564His Uncertain significance ★ ⚠ same condition
GAPVD1 p.Ile1456Val Uncertain significance ★ ⚠ same condition
GAPVD1 c.1251+7G>A Likely benign same condition
GAPVD1 c.1441+17G>T Likely benign same condition
GAPVD1 c.1442-8T>C Likely benign same condition
GAPVD1 c.2428+10G>A Likely benign 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/gapvd1-p-ser112phe (accessed [today's date]).

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