Is AHSG p.Val142Leu (c.424G>T) pathogenic?

AHSG p.Val142Leu (c.424G>T) is classified Benign in AHSG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-13). AlphaMissense: ambiguous (0.4028); Low-frequency (popmax 1.44%, afr).

How common is AHSG p.Val142Leu (c.424G>T) in the general population?

AHSG p.Val142Leu (c.424G>T) is low-frequency (popmax 1.44%, afr) (gnomAD).

What do computational predictors say about AHSG p.Val142Leu (c.424G>T)?

AlphaMissense predicts ambiguous (score 0.4028) — an in-silico prediction, not a clinical call.

AHSG p.Val142Leu

c.424G>T · rs7633550 · VCV786026

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4028 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.44%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4028	ambiguous
REVEL	0.046	moderately benign-leaning
SaProt	LLR -8.11	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,785 bp · p 0.66 · regional, not allelic
Overall
CADD	17.16	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 1.44% African / African-American · 1,080/75,004 alleles

Filtering AF 1.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.34%

Overall 0.0757% 1,220/1,612,028 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.44%	69
Middle Eastern	0.092%	1,087
Admixed American	0.0917%	1,090
Remaining individualsnot grpmax-eligible	0.085%	1,177
South Asian	0.0033%	30,306
European (non-Finnish)	0.00204%	49,130

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.Val142Leu
Coding: c.424G>T
MANE Select: NM_001622
dbSNP: rs7633550
Type: single nucleotide variant
Location: chr3:186617201 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.59
Residue 142: a disulfide bond; a UniProt-annotated variant site (in)

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.Arg317His Likely pathogenic ★ ⚠ same type
AHSG p.Ala139Asp 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/ahsg-p-val142leu (accessed [today's date]).

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