Is POMP p.Val104Ala (c.311T>C) pathogenic?

POMP p.Val104Ala (c.311T>C) is classified Uncertain significance in POMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). AlphaMissense: likely pathogenic (0.5984); Ultra-rare (popmax 0.0117%, amr).

How common is POMP p.Val104Ala (c.311T>C) in the general population?

POMP p.Val104Ala (c.311T>C) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about POMP p.Val104Ala (c.311T>C)?

AlphaMissense predicts likely pathogenic (score 0.5984) — an in-silico prediction, not a clinical call.

POMP p.Val104Ala

c.311T>C · rs753242778 · VCV1982125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5984 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5984	likely pathogenic
REVEL	0.057	moderately benign-leaning
SaProt	LLR -9.85	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 19 kb · p 0.048 · regional, not allelic
Overall
CADD	21.5	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 0.0117% Admixed American · 7/59,994 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000497% 8/1,610,780 alleles · ultra-rare exomes 7/1,458,602 · genomes 1/152,178 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,571
European (non-Finnish)	8.5e-05%	1,177,126

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: POMP
Protein: p.Val104Ala
Coding: c.311T>C
MANE Select: NM_015932
dbSNP: rs753242778
Type: single nucleotide variant
Location: chr13:28672385 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 81.76 · 11 PDB
Residue 104: an α-helix

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

Similar variants

POMP p.Val104Ile Uncertain significance ★ ⚠ same residue
POMP p.Arg32Gln Uncertain significance ★★ ⚠ same type
POMP p.Arg32Trp Uncertain significance ★★ ⚠ same type
POMP p.Asn108His Uncertain significance ★★ ⚠ same type
POMP p.Asn40Ser Uncertain significance ★★ ⚠ same type
POMP p.Gln56His Uncertain significance ★★ ⚠ same type
POMP p.His28Pro Uncertain significance ★★ ⚠ same type
POMP p.Ile112Val Uncertain significance ★★ ⚠ 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/pomp-p-val104ala (accessed [today's date]).

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