Is AHSG p.Pro261Arg (c.782C>G) pathogenic?

AHSG p.Pro261Arg (c.782C>G) is classified Benign in AHSG (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0974); Rare (popmax 0.675%, afr).

How common is AHSG p.Pro261Arg (c.782C>G) in the general population?

AHSG p.Pro261Arg (c.782C>G) is rare (popmax 0.675%, afr) (gnomAD).

What do computational predictors say about AHSG p.Pro261Arg (c.782C>G)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

AHSG p.Pro261Arg

c.782C>G · rs35890379 · VCV747405

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.675%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -8.80	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 2.9	GERP 1.1, phastCons 0.042
Regional constraint	o/e 1.02	unconstrained · MANE · 7,785 bp · p 0.66 · regional, not allelic
Overall
CADD	16.41	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 0.675% African / African-American · 505/74,852 alleles

Filtering AF 0.626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.607%

Overall 0.0357% 573/1,604,656 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.675%	148
Admixed American	0.0619%	1,616
Remaining individualsnot grpmax-eligible	0.0322%	3,101
South Asian	0.0011%	90,894
European (non-Finnish)	0.000853%	117,222

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: AHSG
Protein: p.Pro261Arg
Coding: c.782C>G
MANE Select: NM_001622
dbSNP: rs35890379
Type: single nucleotide variant
Location: chr3:186620608 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.59
Residue 261: a disulfide bond; the 'disordered' region

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

Similar variants

AHSG p.Val342Met Uncertain significance ★★ ⚠ same type
AHSG p.Ala170= Benign/Likely benign ★★ same type
AHSG p.Arg317Cys Benign ★★ ⚠ same type
AHSG p.Met248Thr Benign ★★ same type
AHSG p.Ser256Thr Benign ★★ same type
AHSG p.Thr270= Benign ★★ same type
AHSG p.Val142Leu Benign ★★ ⚠ same type
AHSG p.Arg317His 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/ahsg-p-pro261arg (accessed [today's date]).

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