Is CD1C p.Ile317Thr (c.950T>C) pathogenic?

CD1C p.Ile317Thr (c.950T>C) is classified Uncertain significance in CD1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: likely benign (0.067); Ultra-rare (popmax 0.0465%, nfe).

How common is CD1C p.Ile317Thr (c.950T>C) in the general population?

CD1C p.Ile317Thr (c.950T>C) is ultra-rare (popmax 0.0465%, nfe) (gnomAD).

What do computational predictors say about CD1C p.Ile317Thr (c.950T>C)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

CD1C p.Ile317Thr

c.950T>C · rs114356245 · VCV2454756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0465%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -7.1	GERP -2.8
Regional constraint	o/e 1.06	unconstrained · MANE · 3,408 bp · p 0.27 · regional, not allelic
Overall
CADD	0.224	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 0.0465% European (non-Finnish) · 549/1,179,960 alleles

Filtering AF 0.0433% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.042%

Overall 0.0378% 610/1,614,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0465%	2,149
Remaining individualsnot grpmax-eligible	0.0368%	2,718
Admixed American	0.03%	3,335
South Asian	0.0143%	7,006
African / African-American	0.00933%	10,722

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: CD1C
Protein: p.Ile317Thr
Coding: c.950T>C
MANE Select: NM_001764 · reported on NM_001765
dbSNP: rs114356245
Type: single nucleotide variant
Location: chr1:158293272 (GRCh38)

Full CD1C 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/cd1c-p-ile317thr (accessed [today's date]).

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