Is CLBA1 p.Arg211His (c.632G>A) pathogenic?

CLBA1 p.Arg211His (c.632G>A) is classified Uncertain significance in CLBA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely benign (0.07); Ultra-rare (popmax 0.0294%, afr).

How common is CLBA1 p.Arg211His (c.632G>A) in the general population?

CLBA1 p.Arg211His (c.632G>A) is ultra-rare (popmax 0.0294%, afr) (gnomAD).

What do computational predictors say about CLBA1 p.Arg211His (c.632G>A)?

AlphaMissense predicts likely benign (score 0.07) — an in-silico prediction, not a clinical call.

CLBA1 p.Arg211His

c.632G>A · rs369004416 · VCV3145332

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.07 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.07	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -6.49	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 3.3	GERP 1.1, phastCons 0.42
Regional constraint	o/e 1.09	unconstrained · MANE · 8,324 bp · p 0.057 · regional, not allelic
Overall
CADD	13.43	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 0.0294% African / African-American · 22/74,904 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00198% 32/1,613,830 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0294%	3,405
Admixed American	0.00334%	29,981
Remaining individualsnot grpmax-eligible	0.0032%	31,238
East Asian	0.00223%	44,894
South Asian	0.0011%	91,068
European (non-Finnish)	0.000339%	294,980

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: CLBA1
Protein: p.Arg211His
Coding: c.632G>A
MANE Select: NM_174891
dbSNP: rs369004416
Type: single nucleotide variant
Location: chr14:104991553 (GRCh38)
Gene constraint: LOEUF 1.333 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.43

Full CLBA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLBA1 p.Asp165His Uncertain significance ★ ⚠ same type
CLBA1 p.Gly8Arg Uncertain significance ★ ⚠ same type
CLBA1 p.Leu196Arg Uncertain significance ★ ⚠ same type
CLBA1 p.Ser258Cys Uncertain significance ★ ⚠ same type
CLBA1 p.Ile157Val Likely benign ★ 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/clba1-p-arg211his (accessed [today's date]).

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