Is CTLA4 p.Ser62Phe (c.185C>T) pathogenic?

CTLA4 p.Ser62Phe (c.185C>T) is classified Uncertain significance in CTLA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-28). AlphaMissense: likely benign (0.102); Very rare (popmax 0.00167%, amr).

How common is CTLA4 p.Ser62Phe (c.185C>T) in the general population?

CTLA4 p.Ser62Phe (c.185C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CTLA4 p.Ser62Phe (c.185C>T)?

AlphaMissense predicts likely benign (score 0.102) — an in-silico prediction, not a clinical call.

CTLA4 p.Ser62Phe

c.185C>T · VCV4526173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.102	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.28	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 4	GERP 0.55, phastCons 0.41
Regional constraint	o/e 0.66	unconstrained · MANE · 2,198 bp · p 3.2e-07 · regional, not allelic
Overall
CADD	18.27	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 0.00167% Admixed American · 1/60,030 alleles

Overall 6.84e-05% 1/1,461,892 alleles · very rare

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: CTLA4
Protein: p.Ser62Phe
Coding: c.185C>T
MANE Select: NM_005214
Type: single nucleotide variant
Location: chr2:203870661 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.67 · 22 PDB
Residue 62: a disulfide bond; an α-helix; the ig-like v-type domain

Full CTLA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTLA4 p.Arg51Ter Pathogenic ★★★ same type
CTLA4 p.Arg75Trp Pathogenic ★★★ ⚠ same type
CTLA4 p.Asp153Asn Pathogenic ★★★ ⚠ same type
CTLA4 p.Cys35Ter Pathogenic ★★★ same type
CTLA4 p.Pro136Ala Likely pathogenic ★★★ same type
CTLA4 p.Pro136Leu Likely pathogenic ★★★ same type
CTLA4 p.Pro136Ser Likely pathogenic ★★★ same type
CTLA4 p.Pro137Arg Likely pathogenic ★★★ 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/ctla4-p-ser62phe (accessed [today's date]).

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