Is AASDH p.Phe980Ser (c.2939T>C) pathogenic?

AASDH p.Phe980Ser (c.2939T>C) is classified Uncertain significance in AASDH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: likely pathogenic (0.9442); Very rare (popmax 0.00667%, afr).

How common is AASDH p.Phe980Ser (c.2939T>C) in the general population?

AASDH p.Phe980Ser (c.2939T>C) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about AASDH p.Phe980Ser (c.2939T>C)?

AlphaMissense predicts likely pathogenic (score 0.9442) — an in-silico prediction, not a clinical call.

AASDH p.Phe980Ser

c.2939T>C · rs1057149806 · VCV2527771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9442 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9442	likely pathogenic · top 4% in AASDH
REVEL	0.552	indeterminate
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 46 kb · p 0.076 · regional, not allelic
Overall
CADD	27.7	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 0.00667% African / African-American · 5/74,928 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00031% 5/1,614,046 alleles · very rare

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: AASDH
Protein: p.Phe980Ser
Coding: c.2939T>C
MANE Select: NM_181806
dbSNP: rs1057149806
Type: single nucleotide variant
Location: chr4:56338760 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.50

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

Similar variants

AASDH p.Ile61Val Benign ★★ same type
AASDH p.Ala274Val Uncertain significance ★ ⚠ same type
AASDH p.Ala643Asp Uncertain significance ★ ⚠ same type
AASDH p.Ala643Thr Uncertain significance ★ ⚠ same type
AASDH p.Ala705Gly Uncertain significance ★ ⚠ same type
AASDH p.Ala878Thr Uncertain significance ★ ⚠ same type
AASDH p.Ala880Thr Uncertain significance ★ ⚠ same type
AASDH p.Arg1019Thr 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/aasdh-p-phe980ser (accessed [today's date]).

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