Is CD247 p.Arg164His (c.491G>A) pathogenic?

CD247 p.Arg164His (c.491G>A) is classified Uncertain significance in CD247 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-05). AlphaMissense: likely benign (0.2421); Ultra-rare (popmax 0.0916%, amr); Associated with immunodeficiency 25.

What condition is associated with CD247 p.Arg164His (c.491G>A)?

CD247 p.Arg164His (c.491G>A) is associated with immunodeficiency 25 (ClinVar).

How common is CD247 p.Arg164His (c.491G>A) in the general population?

CD247 p.Arg164His (c.491G>A) is ultra-rare (popmax 0.0916%, amr) (gnomAD).

What do computational predictors say about CD247 p.Arg164His (c.491G>A)?

AlphaMissense predicts likely benign (score 0.2421) — an in-silico prediction, not a clinical call.

CD247 p.Arg164His

Q: How is T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.491G>A · rs201937405 · VCV626075

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2421 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0916%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 25

Computational evidence

Protein change
AlphaMissense	0.2421	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -10.11	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 87 kb · p 0.18 · regional, not allelic
Overall
CADD	29.2	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 0.0916% Admixed American · 55/60,022 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0653%

Overall 0.00508% 82/1,613,832 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0916%	1,091
Remaining individualsnot grpmax-eligible	0.0048%	20,833
European (non-Finnish)	0.00195%	51,293
South Asian	0.0011%	91,072

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: CD247
Protein: p.Arg164His
Coding: c.491G>A
MANE Select: NM_198053
dbSNP: rs201937405
Type: single nucleotide variant
Location: chr1:167431685 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 62.36 · 38 PDB

Full CD247 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 25 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CD247 p.Arg164Cys Uncertain significance ★ ⚠ same residue
CD247 p.Gln101Ter Pathogenic/Likely pathogenic ★★ same condition
CD247 c.58+6G>T Uncertain significance ★★ same condition
CD247 p.Ala120Val Uncertain significance ★★ ⚠ same condition
CD247 p.Ala63Pro Uncertain significance ★★ ⚠ same condition
CD247 p.Ala9Thr Uncertain significance ★★ ⚠ same condition
CD247 p.Arg103Lys Uncertain significance ★★ ⚠ same condition
CD247 p.Arg132Cys Uncertain significance ★★ ⚠ same condition

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/cd247-p-arg164his (accessed [today's date]).

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