Is AHSG p.Val268= (c.804C>T) pathogenic?

AHSG p.Val268= (c.804C>T) is classified Likely benign in AHSG (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-01). Rare (popmax 0.244%, sas).

How common is AHSG p.Val268= (c.804C>T) in the general population?

AHSG p.Val268= (c.804C>T) is rare (popmax 0.244%, sas) (gnomAD).

AHSG p.Val268=

c.804C>T · rs144873304 · VCV2654334

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.244%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.3	GERP -3.9
Overall
CADD	0.296	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.244% South Asian · 222/91,030 alleles

Filtering AF 0.218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.207%

Overall 0.174% 2,805/1,612,762 alleles · rare exomes 2,560/1,460,548 · genomes 245/152,214 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.428%	234
Ashkenazi Jewishnot grpmax-eligible	0.352%	284
South Asiangrpmax	0.244%	410
European (non-Finnish)	0.175%	570
Remaining individualsnot grpmax-eligible	0.175%	573
Admixed American	0.0267%	3,749
Middle Eastern	0.0165%	6,052
African / African-American	0.0147%	6,818

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val268=
Coding: c.804C>T
MANE Select: NM_001622
dbSNP: rs144873304
Type: single nucleotide variant
Location: chr3:186620630 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.59
Residue 268: 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-val268 (accessed [today's date]).

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