Is CD1A p.Ala306Val (c.917C>T) pathogenic?

CD1A p.Ala306Val (c.917C>T) is classified Uncertain significance in CD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.1265); Ultra-rare (popmax 0.0856%, sas).

How common is CD1A p.Ala306Val (c.917C>T) in the general population?

CD1A p.Ala306Val (c.917C>T) is ultra-rare (popmax 0.0856%, sas) (gnomAD).

What do computational predictors say about CD1A p.Ala306Val (c.917C>T)?

AlphaMissense predicts likely benign (score 0.1265) — an in-silico prediction, not a clinical call.

CD1A p.Ala306Val

c.917C>T · rs199910842 · VCV2561868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1265 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0856%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1265	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -3	GERP 0.76
Regional constraint	o/e 1.13	unconstrained · MANE · 3,017 bp · p 0.0086 · regional, not allelic
Overall
CADD	15.48	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 0.0856% South Asian · 78/91,070 alleles

Filtering AF 0.0703% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0646%

Overall 0.0103% 167/1,613,986 alleles · ultra-rare exomes 157/1,461,728 · genomes 10/152,258 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0856%	1,168
Admixed American	0.0367%	2,728
Remaining individualsnot grpmax-eligible	0.016%	6,250
European (non-Finnish)	0.00449%	22,262
East Asian	0.00446%	22,442
Finnishnot grpmax-eligible	0.00312%	32,012

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: CD1A
Protein: p.Ala306Val
Coding: c.917C>T
MANE Select: NM_001763
dbSNP: rs199910842
Type: single nucleotide variant
Location: chr1:158257454 (GRCh38)
Gene constraint: LOEUF 1.644 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.11 · 16 PDB

Full CD1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD1A c.605-3C>T Benign ★★ same type
CD1A p.Arg90Cys Benign ★★ same type
CD1A p.Gly240Asp Likely benign ★★ ⚠ same type
CD1A p.Ala102Thr Uncertain significance ★ ⚠ same type
CD1A p.Ala196Glu Uncertain significance ★ ⚠ same type
CD1A p.Ala196Ser Uncertain significance ★ ⚠ same type
CD1A p.Ala264Pro Uncertain significance ★ ⚠ same type
CD1A p.Arg185Cys 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/cd1a-p-ala306val (accessed [today's date]).

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