Is C2CD4A p.Thr202Ala (c.604A>G) pathogenic?

C2CD4A p.Thr202Ala (c.604A>G) is classified Likely benign in C2CD4A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0565); Very rare (popmax 0.00165%, sas).

How common is C2CD4A p.Thr202Ala (c.604A>G) in the general population?

C2CD4A p.Thr202Ala (c.604A>G) is very rare (popmax 0.00165%, sas) (gnomAD).

What do computational predictors say about C2CD4A p.Thr202Ala (c.604A>G)?

AlphaMissense predicts likely benign (score 0.0565) — an in-silico prediction, not a clinical call.

C2CD4A p.Thr202Ala

c.604A>G · rs772478979 · VCV3135881

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0565 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00165%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0565	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -4.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.26	GERP -2.5
Regional constraint	o/e 1.06	unconstrained · MANE · 1,106 bp · p 0.13 · regional, not allelic
Overall
CADD	3.989	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 0.00165% South Asian · 1/60,680 alleles

Filtering AF 0.000686% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000529%

Overall 0.00132% 16/1,213,542 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00197%	50,764
South Asiangrpmax	0.00165%	60,680
African / African-American	0.00152%	65,914
European (non-Finnish)	0.00123%	81,298

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: C2CD4A
Protein: p.Thr202Ala
Coding: c.604A>G
MANE Select: NM_207322
dbSNP: rs772478979
Type: single nucleotide variant
Location: chr15:62068217 (GRCh38)
Gene constraint: LOEUF 1.963 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.36
Residue 202: the 'disordered' region

Full C2CD4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD4A p.Thr202Ile Uncertain significance ★ ⚠ same residue
C2CD4A p.Ala102Thr Uncertain significance ★ ⚠ same type
C2CD4A p.Ala160Thr Uncertain significance ★ ⚠ same type
C2CD4A p.Ala192Glu Uncertain significance ★ ⚠ same type
C2CD4A p.Ala226Asp Uncertain significance ★ ⚠ same type
C2CD4A p.Ala318Thr Uncertain significance ★ ⚠ same type
C2CD4A p.Ala318Val Uncertain significance ★ ⚠ same type
C2CD4A p.Ala338Val 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/c2cd4a-p-thr202ala (accessed [today's date]).

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