Is AMDHD1 p.Ala339Val (c.1016C>T) pathogenic?

AMDHD1 p.Ala339Val (c.1016C>T) is classified Uncertain significance in AMDHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.3237); Absent from gnomAD v4.1.

How common is AMDHD1 p.Ala339Val (c.1016C>T) in the general population?

AMDHD1 p.Ala339Val (c.1016C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMDHD1 p.Ala339Val (c.1016C>T)?

AlphaMissense predicts likely benign (score 0.3237) — an in-silico prediction, not a clinical call.

AMDHD1 p.Ala339Val

c.1016C>T · rs2499619849 · VCV3114945

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3237 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3237	likely benign
REVEL	0.57	indeterminate
SaProt	LLR -7.12	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 24 kb · p 0.15 · regional, not allelic
Overall
CADD	26.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AMDHD1
Protein: p.Ala339Val
Coding: c.1016C>T
MANE Select: NM_152435
dbSNP: rs2499619849
Type: single nucleotide variant
Location: chr12:95965763 (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.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
AMDHD1 p.Arg136Cys 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-ala339val (accessed [today's date]).

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