Is AHSG p.Pro30Leu (c.89C>T) pathogenic?

AHSG p.Pro30Leu (c.89C>T) is classified Likely benign in AHSG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.0767); Very rare (popmax 0.00659%, sas).

How common is AHSG p.Pro30Leu (c.89C>T) in the general population?

AHSG p.Pro30Leu (c.89C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about AHSG p.Pro30Leu (c.89C>T)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

AHSG p.Pro30Leu

c.89C>T · rs377000409 · VCV2234752

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -4.92	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 -1.9	GERP -4.8
Regional constraint	o/e 1.02	unconstrained · MANE · 7,785 bp · p 0.66 · regional, not allelic
Overall
CADD	0.102	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 0.00659% South Asian · 6/91,084 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000805% 13/1,614,018 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,181
African / African-American	0.00133%	74,910
European (non-Finnish)	0.000508%	196,672

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.Pro30Leu
Coding: c.89C>T
MANE Select: NM_001622
dbSNP: rs377000409
Type: single nucleotide variant
Location: chr3:186613230 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.59
Residue 30: the cystatin fetuin-a-type 1 domain

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-pro30leu (accessed [today's date]).

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