Is CD1A p.Arg185His (c.554G>A) pathogenic?

CD1A p.Arg185His (c.554G>A) is classified Uncertain significance in CD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-22). AlphaMissense: likely benign (0.1081); Rare (popmax 0.148%, mid).

How common is CD1A p.Arg185His (c.554G>A) in the general population?

CD1A p.Arg185His (c.554G>A) is rare (popmax 0.148%, mid) (gnomAD).

What do computational predictors say about CD1A p.Arg185His (c.554G>A)?

AlphaMissense predicts likely benign (score 0.1081) — an in-silico prediction, not a clinical call.

CD1A p.Arg185His

c.554G>A · rs142655599 · VCV2360688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1081 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1081	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.15	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 -7.2	GERP -3.6
Regional constraint	o/e 1.13	unconstrained · MANE · 3,017 bp · p 0.0086 · regional, not allelic
Overall
CADD	15.32	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 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.017% 275/1,614,092 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	674
Ashkenazi Jewishnot grpmax-eligible	0.122%	822
Remaining individualsnot grpmax-eligible	0.0304%	3,290
Admixed American	0.0217%	4,617
European (non-Finnish)	0.0161%	6,211
African / African-American	0.00666%	15,006
East Asian	0.00223%	44,876
Finnishnot grpmax-eligible	0.00156%	63,992
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: CD1A
Protein: p.Arg185His
Coding: c.554G>A
MANE Select: NM_001763
dbSNP: rs142655599
Type: single nucleotide variant
Location: chr1:158256232 (GRCh38)
Gene constraint: LOEUF 1.644 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.11 · 16 PDB
Residue 185: an α-helix; the ig-like domain

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

Similar variants

CD1A p.Arg185Cys Uncertain significance ★ ⚠ same residue
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

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-arg185his (accessed [today's date]).

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