Is ELMOD1 p.Ala221Val (c.662C>T) pathogenic?

ELMOD1 p.Ala221Val (c.662C>T) is classified Uncertain significance in ELMOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.0859); Absent from gnomAD v4.1.

How common is ELMOD1 p.Ala221Val (c.662C>T) in the general population?

ELMOD1 p.Ala221Val (c.662C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELMOD1 p.Ala221Val (c.662C>T)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

ELMOD1 p.Ala221Val

c.662C>T · rs867575085 · VCV2554056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.38	acceptor loss, 14 bp away · masked 0 · deltas
Pangolin	Δ0.34	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.4	GERP 1.8, phastCons 0.99
Regional constraint	o/e 0.85	unconstrained · MANE · 47 kb · p 0.0031 · regional, not allelic
Overall
CADD	18.01	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: ELMOD1
Protein: p.Ala221Val
Coding: c.662C>T
MANE Select: NM_018712
dbSNP: rs867575085
Type: single nucleotide variant
Location: chr11:107654186 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 90.80
Residue 221: the elmo domain

Full ELMOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMOD1 p.Ala117Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala188Val Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala231Pro Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala326Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala76Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Arg113Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Arg123Leu Uncertain significance ★ ⚠ same type
ELMOD1 p.Arg154Trp 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/elmod1-p-ala221val (accessed [today's date]).

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