Is CORO7-PAM16 p.Ala403Val (c.1208C>T) pathogenic?

CORO7-PAM16 p.Ala403Val (c.1208C>T) is classified Uncertain significance in CORO7-PAM16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.0661); Ultra-rare (popmax 0.034%, eas).

How common is CORO7-PAM16 p.Ala403Val (c.1208C>T) in the general population?

CORO7-PAM16 p.Ala403Val (c.1208C>T) is ultra-rare (popmax 0.034%, eas) (gnomAD).

What do computational predictors say about CORO7-PAM16 p.Ala403Val (c.1208C>T)?

AlphaMissense predicts likely benign (score 0.0661) — an in-silico prediction, not a clinical call.

CORO7-PAM16 p.Ala403Val

c.1208C>T · VCV4232964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0661 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0661	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.7	GERP -2.9
Overall
CADD	0.061	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 0.034% East Asian · 15/44,054 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0169%

Overall 0.00209% 32/1,531,974 alleles · ultra-rare exomes 28/1,379,630 · genomes 4/152,344 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.034%	2,937
Admixed American	0.00871%	11,477
South Asian	0.00647%	15,446
European (non-Finnish)	0.0007%	142,929

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: CORO7-PAM16
Protein: p.Ala403Val
Coding: c.1208C>T
Type: single nucleotide variant
Location: chr16:4364343 (GRCh38)

Full CORO7-PAM16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/coro7-pam16-p-ala403val (accessed [today's date]).

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