Is AMDHD1 p.Val327Ile (c.979G>A) pathogenic?

AMDHD1 p.Val327Ile (c.979G>A) is classified Uncertain significance in AMDHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.1089); Rare (popmax 0.109%, amr).

How common is AMDHD1 p.Val327Ile (c.979G>A) in the general population?

AMDHD1 p.Val327Ile (c.979G>A) is rare (popmax 0.109%, amr) (gnomAD).

What do computational predictors say about AMDHD1 p.Val327Ile (c.979G>A)?

AlphaMissense predicts likely benign (score 0.1089) — an in-silico prediction, not a clinical call.

AMDHD1 p.Val327Ile

c.979G>A · rs143399547 · VCV3114971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1089 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.109%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1089	likely benign
REVEL	0.385	indeterminate
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.95, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 24 kb · p 0.15 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% Admixed American · 65/59,832 alleles

Filtering AF 0.0874% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0798%

Overall 0.00421% 68/1,613,294 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.109%	920
Remaining individualsnot grpmax-eligible	0.0016%	62,442
African / African-American	0.00133%	74,994
European (non-Finnish)	8.48e-05%	1,179,759

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: AMDHD1
Protein: p.Val327Ile
Coding: c.979G>A
MANE Select: NM_152435
dbSNP: rs143399547
Type: single nucleotide variant
Location: chr12:95965726 (GRCh38)
Gene constraint: LOEUF 1.381 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.23

Full AMDHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMDHD1 p.Ala107Gly Uncertain significance ★ ⚠ same type
AMDHD1 p.Ala20Asp Uncertain significance ★ ⚠ same type
AMDHD1 p.Ala302Pro Uncertain significance ★ ⚠ same type
AMDHD1 p.Ala339Val Uncertain significance ★ ⚠ same type
AMDHD1 p.Ala35Ser Uncertain significance ★ ⚠ same type
AMDHD1 p.Ala364Asp Uncertain significance ★ ⚠ same type
AMDHD1 p.Ala373Val Uncertain significance ★ ⚠ same type
AMDHD1 p.Ala56Pro 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/amdhd1-p-val327ile (accessed [today's date]).

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