Is CCDC91 p.Arg53His (c.158G>A) pathogenic?

CCDC91 p.Arg53His (c.158G>A) is classified Likely benign in CCDC91 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-26). AlphaMissense: likely benign (0.0545); Ultra-rare (popmax 0.011%, sas).

How common is CCDC91 p.Arg53His (c.158G>A) in the general population?

CCDC91 p.Arg53His (c.158G>A) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about CCDC91 p.Arg53His (c.158G>A)?

AlphaMissense predicts likely benign (score 0.0545) — an in-silico prediction, not a clinical call.

CCDC91 p.Arg53His

c.158G>A · rs368981349 · VCV2530922

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0545 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0545	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.22	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 2.8	GERP -0.38, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 292 kb · p 0.81 · regional, not allelic
Overall
CADD	14.39	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 0.011% South Asian · 10/91,052 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00291% 47/1,612,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,105
East Asian	0.00892%	11,209
Remaining individualsnot grpmax-eligible	0.0048%	20,813
European (non-Finnish)	0.00229%	43,683
Admixed American	0.00167%	59,920
Finnishnot grpmax-eligible	0.00156%	63,950
African / African-American	0.00134%	74,782

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: CCDC91
Protein: p.Arg53His
Coding: c.158G>A
MANE Select: NM_018318
dbSNP: rs368981349
Type: single nucleotide variant
Location: chr12:28305697 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 76.04 · 1 PDB

Full CCDC91 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC91 p.Asp121Gly Benign ★★ same type
CCDC91 p.Gln403Lys Benign ★★ same type
CCDC91 p.Ala127Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala181Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala209Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala219Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala28Ser Uncertain significance ★ ⚠ same type
CCDC91 p.Ala334Gly 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/ccdc91-p-arg53his (accessed [today's date]).

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